NYU School of Medicine responds to PAR-12-126, proposing to compare persistent organic pollutant (POP) biomarkers in World Trade Center-exposed adolescents to a matched group, and to assess associations of POP biomarkers with cardiometabolic and renal outcomes. The World Trade Center (WTC) disaster released large amounts of polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs) and perfluorinated compounds (PFCs), depositing widely. Increases in biomarkers of PCDDs and PCDFs have been identified among responders, firefighters and pregnant women, compared with nationally representative samples. Responders have also been identified to have higher PFC biomarkers than nationally representative samples, as well as higher levels of PFCs in relationship to WTC dust/smoke exposure. Children have unique physiology and behaviors that may have heightened exposure, especially from resuspended dust in homes with contaminated ventilation systems and carpets, and proximity to fires which continued for >3 months afterwards, precipitating ongoing release of combustion products. Yet, biomarkers of PCDD/PCDFs and PFCs have not been assessed in children who lived/attended school in lower Manhattan and likely had higher acute, subchronic and chronic exposures. The biological persistence of PFCs (4-8 year half-life) and PCDD/PCDFs (7-15 half-life) poses unique concerns for adolescents exposed to the disaster. Because they may mobilize highly lipophilic chemicals that were absorbed into fatty stores earlier in life, these adolescents may experience enhanced vulnerability and potentially acutely increasing toxicity to multiple organ systems at this stage of life. The WTC Adolescent Health Study (U01OH010394) is recruiting 225 12-19 year olds who previously participated in the WTC Health Registry, and comparing fasting lipids, insulin resistance, blood pressure, brachial artery distensibility, and central aortic stiffness toa matched comparison group of 225 adolescents. We propose an ancillary study, capitalizing on banked biospecimens, stored at -80oC, to measure PFCs and PCDD/PCDFs in the two groups and assess relationships of PFCs and PCDD/PCDFs to cardiometabolic and renal outcomes. Preliminary data identify a remarkably high frequency of cardiometabolic risk factors among WTC-exposed children, and relationships of subchronic dust exposures to hypertriglyceridemia and lower levels of the cardioprotective high-density lipoprotein (HDL), as well as associations of PFCs with reduced eGFR and hyperuricemia in a national sample of adolescents. The study is led by an internationally known expert in children's environmental health who provides clinical care to children with World Trade Center-related health concerns and exposures, and the research team benefits from strong partnerships with community- based organizations who have provided outreach and support to affected communities since 2001, which will enhance recruitment and communication of results.